Microdialysis (MD) is an increasingly important tool for sampling the extracellular fluid of specific regions of the brain. Real time, direct analysis of the microdialysate would be advantageous for studying dynamic changes in brain chemistry as a function of behavior, or in response to experimental paradigms or trauma. The proposed research will develop a surface enhanced Raman spectroscopy (SERS) probe on the tip of an optic fiber in dimensions suitable for insertion into an in vivo microdialysis cannula. the SERS/MD probe will enable in vivo analysis of neurotransmitters or other substance in brain extracellular fluid by SERS techniques. The Phase I objectives are to fabricate optical fibers with SERS substrates, couple them with microdialysis cannulas, and demonstrate dopamine analysis during microdialysis from a simulated brain extracellular fluid. Successful demonstration of the feasibility of a SERS/MD probe will provide a foundation for Phase II work to evaluate the probe during in vivo microdialysis experiments and to develop a prototype SERS/MD probe and instrumentation package for use in academic, clinical and pharmaceutical neurochemistry laboratories.